METHOD OF MANUFACTURING SOLID SOLUTION PEFORATOR PATCHES AND USES THEREOF

• US 20110121486A1
• Filed: 05/21/2009
• Published: 05/26/2011
• Est. Priority Date: 05/21/2008
• Status: Active Grant

• Current Assignee: TheraJect, Inc.
• Original Assignee: TheraJect, Inc.
• Inventors: Kwon, Sung-Yun, Oh, Sea-Jin
• Granted Patent: US 9,381,680 B2
• Time in Patent Office: Days
• US Class Current: 264/225
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• CPC Class Codes: A61B 2017/00345 Micromachines, nanomachines, microsystems
• CPC Class Codes: A61B 2017/00761 Removing layer of skin tissue, e.g. wrinkles, scars or cancerous tissue
• CPC Class Codes: A61M 2037/0023 Drug applicators using microneedles
• CPC Class Codes: A61M 2037/0046 Solid microneedles
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: B29C 33/0027 with deep narrow cavities, e.g. for making piles non-woven pile fabrics D04H11/00
• CPC Class Codes: B29C 33/0033 constructed for making articles provided with holes
• CPC Class Codes: B29C 33/308 Adjustable moulds for injection moulding B29C45/376
• CPC Class Codes: B29C 33/3878 used as masters for making successive impressions
• CPC Class Codes: B29C 33/3885 the mould parts being co-operating impressions

Abstract

Methods for fabricating and manufacturing solid solution perforators (SSPs) using sharp metal or glass needles and/or subsequent molding and use are described. The methods entail making microneedles by various precision machining techniques and micromold structures from curable materials. Various designs of patch, cartridge and applicator are described. Also described are methods for adjusting the microneedle mechanical strength using formulation and/or post-drying processes.

Claims

1. A method of manufacturing a microneedle array comprising:

(a) preparing a positive master mold by positioning microneedles in a defining plate comprising a top and bottom surface, wherein the microneedles are placed at a predetermined distance from one another, and further wherein the microneedle tips protrude from the bottom of the defining plate;

(b) preparing a negative mold by either casting a castable material onto the positive master mold or dipping the positive master mold into a curable gel or thermoplastic material, to produce a negative mold having the same surface contour as the positive master mold;

(c) adding a dissolvable polymer to the negative mold to form a microneedle array; and

(d) drying the microneedle array.

2. The method of claim 1, wherein all the microneedles positioned in the defining plate protrude the same distance from the bottom of the defining plate.

3. The method of claim 1, wherein at least one of the microneedles positioned in the defining plate protrudes a different distance from the bottom of the defining plate than the other microneedles.

4. The method of claim 1, wherein individual needle lengths in the defining plate are adjusted using an actuator mechanism that moves individual needles to a desired distance through the defining plate.

5. The method of claim 1, wherein the microneedle tip is positioned using a stop wall at a desired distance from the defining plate.

6. The method of claim 1, wherein the microneedle tip is positioned using tapered holes in the defining plate.

7. The method of claim 1, wherein the curable gel or castable material is uncured silicone.

8. The method of claim 1, wherein the curable gel or castable material is polydimethylsilozane (PDMS).

9. The method of claim 1, wherein the dissolvable polymer is a hydrogel.

10. The method of claim 9, wherein the hydrogel comprises sodium carboxymethyl cellulose (SCMC).

11. The method of claim 1, wherein a selected drug is added to the negative mold.

12. The method of claim 1, further comprising applying a vacuum, centrifuge or compressive force to the negative mold to fill the mold with the dissolvable polymer and/or a selected drug.

13. The method of claim 1, further comprising separating the dried microneedle array from the negative mold.

14. A method of manufacturing a microneedle array comprising:

(a) preparing a positive master mold by drilling, milling or grinding a metal or formable plate in a predetermined direction at a predetermined angle to define a plurality of microneedles;

(b) preparing a negative mold by either casting a castable material onto the positive master mold or dipping the positive master mold into a curable gel or thermoplastic material, to produce a negative mold having the same surface contour as the positive master mold;

(c) adding a dissolvable polymer to the negative mold to form a microneedle array; and

(d) drying the microneedle array.

15. The method of claim 14, wherein the drilling, milling or grinding is done using precision machining.

16. The method of claim 15, wherein the drilling, milling or grinding is done by Computer Numerical Control (CNC) milling, grinding or drilling.

17. The method of claim 14, wherein the curable gel or castable material is uncured silicone.

18. The method of claim 14, wherein the curable gel or castable material is polydimethylsilozane.

19. The method of claim 14, wherein the dissolvable polymer is a hydrogel.

20. The method of claim 19, wherein the hydrogel comprises sodium carboxymethyl cellulose (SCMC).

21. The method of claim 14, wherein a selected drug is added to the negative mold.

22. The method of claim 14, wherein the method further comprises casting an adhesive layer between the microneedles of the microneedle array.

23. The method of claim 14, wherein the method further comprises casting a flexible and sticky layer on microneedle array.

24. The method of claim 14, wherein the method further comprises adding vitamin C to the negative mold.

25. The method of claim 14, wherein the method further comprises creating a micro-hole at the microneedle tip of the negative mold.

26. A method of manufacturing a microneedle array system comprising:

(a) manufacturing a microneedle array; and

(b) mounting the manufactured microneedle array in a cartridge for delivery to skin,

wherein the step of (a) manufacturing the microneedle array comprises;

(i) preparing a positive master mold by positioning microneedles in a defining plate comprising a top and bottom surface, wherein the microneedles are placed at a predetermined distance from one another, and further wherein the microneedle tips protrude from the bottom of the defining plate,

(ii) preparing a negative mold by either casting a castable material onto the positive master mold or dipping the positive master mold into a curable gel or thermoplastic material, to produce a negative mold having the same surface contour as the positive master mold,

(iii) adding a dissolvable polymer to the negative mold to form a microneedle array, and

(iv) drying the microneedle array.

27. The method of claim 26, wherein the cartridge is in association with an injector.

28. A method of manufacturing a microneedle array system comprising:

(a) manufacturing a microneedle array; and

(b) mounting the manufactured microneedle array in a cartridge for delivery to skin,

wherein the step of (a) manufacturing the microneedle array comprises;

(i) preparing a positive master mold by drilling, milling or grinding a metal or formable plate in a predetermined direction at a predetermined angle to define a plurality of microneedles,

(ii) preparing a negative mold by either casting a castable material onto the positive master mold or dipping the positive master mold into a curable gel or thermoplastic material, to produce a negative mold having the same surface contour as the positive master mold,

(iii) adding a dissolvable polymer to the negative mold to form a microneedle array, and

(iv) drying the microneedle array.

29. The method of claim 28, wherein the cartridge is in association with an injector.